Genome-wide Discovery of Transcriptome Differences in Parkinson's Neuronal Model

Grant Winners

  • Lubov Nathanson, Ph.D. – College of Osteopathic Medicine
  • Paula Waziry, Ph.D. – College of Osteopathic Medicine
  • Tiffany Cabrera – Farquhar College of Arts and Sciences

Dean

  • Elaine Wallace, D.O. – College of Osteopathic Medicine

Abstract

President Hanbury with Lubov Nathanson, Ph.D. (HPD-OST), Paula Waziry, Ph.D. (HPD-OST), and Tiffany Cabrera (FAR)

Parkinson disease (PD) is the second most common neurodegenerative disorder, affecting 1-2% of the population over the age of 65 (1, 2). The causes of PD are still elusive and to date there is no cure for this disease (3). PD is characterized by the selective and progressive loss of specialized neurons. At the same time, surviving neurons start to show characteristic cellular structures known as Lewy bodies. These structures are aggregations of dysfunctional proteins and lipids, in which a-synuclein is the main component (4). This protein is normally enriched in the adult human brain where it is expressed within glia and neurons (5, 6). a-synuclein participates in signal transduction, and is important in learning and neuronal plasticity (7, 8). Above normal levels of a-synuclein expression in the brain lead to the development of PD (6, 9, 10).

Some effects of a-synuclein aggregation have been identified on metabolic pathways, however not much is known about these pathways. Our collaborators have a well-developed model of PD in form of cultured neurons that can overexpress a-synuclein.  Here we propose an extensive investigation of the regulatory epigenetic mechanisms that are affected by a-synuclein aggregation. In order to accomplish this, we will (Specific Aim I) measure expression of all cellular transcripts using the latest state-of-the-art technology RNAseq, which is an unbiased discovery tool. Furthermore, we will (Specific Aim II) use bioinformatics to correlate gene expression obtained in Specific Aim I for identification of specific pathways that can be further targeted for controlled therapy. Our systematic approach using RNAseq and bioinformatics will most likely reveal previously unknown transcripts that are important for neuronal preservation.  Results of this study will help to develop cellularly targeted PD treatment, which the potential for more effective treatment than the generalized option for neurotransmitter replenishment that is currently available.